ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.475T>C (p.Tyr159His)

gnomAD frequency: 0.00001  dbSNP: rs1305721973
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001221388 SCV001393429 uncertain significance Spastic paraplegia 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 159 of the SACS protein (p.Tyr159His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SACS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV003294062 SCV003976566 uncertain significance Inborn genetic diseases 2023-04-20 criteria provided, single submitter clinical testing The c.475T>C (p.Y159H) alteration is located in exon 7 (coding exon 6) of the SACS gene. This alteration results from a T to C substitution at nucleotide position 475, causing the tyrosine (Y) at amino acid position 159 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001836169 SCV002086755 uncertain significance Charlevoix-Saguenay spastic ataxia 2020-02-13 no assertion criteria provided clinical testing

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